凝血酶激活的纤溶抑制物及其编码基因多态性与冠心病的相关性研究

Genetic polymorphism of thrombin activatable fibrinolysis inhibitor and coronary heart disease

目的研究凝血酶激活的纤溶抑制物(TAFI)及其编码基因多态性与冠心病(CHD)之间的相关性。方法应用聚合酶链反应-限制性内切酶片段长度多态性分析技术(PCR-RFLP)对136例冠心病患者和85名健康对照者的TAFI编码基因Thr325Ile和Thr147Ala的基因多态性进行分析,同时采用酶联免疫吸附试验双抗体夹心法对所有受试者血浆TAFI的抗原及活性水平进行检测,探讨TAFI及其编码基因的基因多态性与CHD的关系。结果健康对照组和CHD组血浆TAFI的抗原与活性水平分别为(72.50±33.95)%、(21.75±13.79)μg/ml和(185.21±89.82)%、(91.29±43.48)μg/ml,两组之间的差异有统计学意义(P<0.01)。在健康对照组和CHD组TAFI编码基因的基因多态性分布中,Thr325Ile编码基因的3种基因型和Thr147Ala编码基因的3种基因型两组之间基因型及等位基因的多态性分布频率差异无统计学意义(P>0.05)。在Thr325Ile编码基因的3种基因型中,Thr325Thr基因型血浆TAFI的抗原水平明显高于其他两种基因型(Thr325Ile和Ile325Ile),差异有统计学意义(Ρ<0.01),而后两种基因型之间差异无统计学意义(P>0.05);Ile325Ile基因型血浆TAFI的活性水平较其他两种基因型(Thr325Thr和Thr325Ile)低,差异有统计学意义(Ρ<0.01),而后两者之间的差异无统计学意义(P>0.05);在Thr147Ala编码基因的3种基因型(Ala147Ala、Ala147Thr和Thr147Thr)之间,血浆TAFI的抗原与活性水平的差异无统计学意义(P>0.05)。结论 TAFI可能是CHD的危险因子;TAFI编码基因Thr325Ile的基因多态性对血浆TAFI的抗原与活性水平有一定的影响,但TAFI的两种编码基因Thr325Ile与Ala147Thr的基因多态性与CHD的发生并无明显的相关性。

Objective To investigate the association between genetic polymorphism of thrombin activatable fibrinolysis inhibitor （TAFI） and coronary heart disease （CHD）.Methods The genetic polymorphism of TAFI genes （Thr325Ile and Ala147Thr） from 136 patients with CHD and 85 healthy subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）.The protein level and the activity of TAFI in plasma were measured by double antibody enzyme linked immunosorbent assay.Results The protein levels and the activity of TAFI in plasma were markedly increased in patients with CHD as compared with healthy subjects [（185.21±89.82）% and （91.29±43.48）μg/ml vs（72.50±33.95）% and （21.75±13.79）μg/ml,P0.01].The genetyping （Thr325Thr,Thr325Ile and Ile325Ile） in healthy subjects and CHD patients respectively.The genetyping（Ala147Ala,Ala147Thr and Thr147Thr） in healthy subjects and CHD patients respectively.No statistical significance was found in gene polymorphism distributions of alleles and genotypes between healthy subjects and CHD patients（P0.05）.Among three genotypes of Thr325Ile,the TAFI antigen of Thr325Thr was higher than that of the other two genotypes （Thr325Ile and Ile325Ile）,there was significant difference between the TAFI antigen of Thr325Thr and that of the others（P0.01）,and no statistical significance between the TAFI antigen of Thr325Ile and that of Ile325Ile（P0.05）.But the TAFI activity of the Ile325Ile was lower than that of the other genotypes（Thr325Thr and Thr325Ile）,there was significantly difference between the TAFI activity of Ile325Ile and that of the others（P0.01）,and no statistical significance between the TAFI activity of Thr325Thr and that of Thr325Ile（P0.05）.Among all genotypes of Thr147Ala,no significant difference was found in the plasma levels of TAFI antigen and activity （P0.05）.Conclusion TAFI may be a risk factor of CHD.The genotype of Thr325Ile may affect the activity and plasma levels of TAFI.There is no correlation between CHD and the genetic polymorphism of Thr325Ile and Thr147Ala.